The purpose of the proposed project is twofold: first, to determine the alterations in the ionic composition of the senescent and cataractous lens and to identify the factors responsible for these changes and second, to attempt to stimulate these changes in young noncataractous lenses in an effort to explore the role of internal cations in lens physiology. The first part of the study is an extension of previous investigations pursued in our laboratory in which the mechanisms of cation regulation have been defined and membrane parameters obtained in young rabbit lenses. In addition to studying processes involved in cation regulation in the senescent lens, similar data will be obtained from lenses of the canine, a species in which senescent cataract appears to develop. An extensive analysis and correlation of cation concentrations and their transport parameters, membrane permeability, bioelectric potential, and activities of translocating enzymes with age is possible with the anticipated availability of a PROPHET computer system capable of multiple correlation analysis. The second phase of the research plan is concerned with the relationship of changes in the ionic composition to alterations in lens physiology. Since the transport systems for Na ion, K ion and in part for Ca ions have been defined in the young, noncataractous lens, it is feasible to selectively alter internal levels of these cations individually and in combination to effect a change in cellular processes such as energy metabolism, transport phenomena, and protein synthesis. The effects of Ca- loading on lens physiology will be studied in some detail. A related problem to be explored is whether the lens has the means to resist changes in intracellular ion concentrations which result from age related alterations in membrane permeability or transport. The degree to which such a feed-back system contributes to cation homeostasis in lenses of different ages will be assessed by measuring stimulated transport rates induced by alterations in internal cation levels.